Department of Pathology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Uniondale, New York.
Department of Pathology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Uniondale, New York.
J Am Soc Cytopathol. 2022 Nov-Dec;11(6):345-351. doi: 10.1016/j.jasc.2022.06.007. Epub 2022 Jul 14.
At present, GATA binding protein 3 (GATA-3) is the most frequently used diagnostic immunohistochemical (IHC) marker for breast carcinoma (BC). However, it is not specific and has very low sensitivity for triple-negative BC (TNBC). SRY-box transcription factor 10 (SOX-10) and trichorhinophalangeal syndrome type 1 (TRPS-1) have been suggested for inclusion in the diagnostic workup of TNBC. TRPS-1 has not been established in cytology specimens as a diagnostic IHC marker for metastatic BC (MBC). Hence, in the present study we evaluated the utility of TRPS-1 in diagnosing MBC in cytology specimens.
MBC cases diagnosed on cytology specimens from January to October 2020 were included in the present study. Only cases with hormonal status available and ≥20 tumor cells on cell blocks were included in the study. The cell blocks were assessed for TRPS-1, GATA-3, and SOX-10 IHC marker positivity (intensity and percentage of tumor cells). The results were correlated with the specimen type (fine needle aspiration [FNA] versus body fluid) and various BC prognostic subgroups.
We analyzed 61 cases, including 33 body fluid and 28 FNA (13 lymph node, 10 bone, 2 liver, 2 soft tissue, and 1 lung) specimens. TRPS-1 had 97.2% positivity in ER/PR+ (estrogen receptor/progesterone receptor-positive) MBC compared with GATA-3, which had 100% positivity in the same group. TRPS-1 showed high positivity in 35 of 37 cases (94.6%) and intermediate positivity in 1 (2.6%) and was negative/low positive in 1 case (2.7%). In contrast, GATA-3 showed high positivity for all 37 cases (100%). SOX-10 showed positivity in only 1 of 37 cases (2.7%), with intermediate positivity. In the HER2+ (human epidermal growth factor receptor 2-positive) group, TRPS-1 showed high positivity in 5 of 7 cases (71.4%), intermediate positivity in 1 case (14.3%), and negativity in 1 case (14.3%). However, GATA-3 showed high positivity in 6 of 7 cases (85.7%) and negative/low positivity in 1 case (14.3%). SOX-10 was negative in all 7 cases. In TNBC, TRPS-1 showed high positivity in 16 of 17 cases (94%) and intermediate positivity in 1 (5.9%), and GATA-3 showed high positivity in 9 (53%), intermediate positivity in 2 (11.8%), and low positive/negative in 6 of the 17 cases (35.3%). TRPS-1 expression was significantly higher than GATA-3 expression for the number of positive cases (P = 0.07), mean percentage of positive tumor cells (P = 0.005), and intensity of reactivity (P = 0.005). SOX-10 expression was present in only 5 of 17 cases (29%), with a mean percentage of positivity in the tumor cells of 26.5% and intensity of 0.8. No differences were found in the IHC results between the different specimen types (FNA versus fluid) in any group.
TRPS-1 is a highly sensitive new diagnostic IHC marker for breast carcinoma, with a similar positivity rate in ER/PR+ and HER2+ BC compared with GATA-3 and a higher positivity rate than GATA-3 and SOX-10 in TNBC in cytology specimens. In particular, when only a few clusters of tumor cells are present on the cell block, TRPS-1 can be highly useful, because its mean percentage of positive tumor cells and intensity are higher than those of other IHC markers.
目前,GATA 结合蛋白 3(GATA-3)是乳腺癌(BC)最常用的诊断免疫组织化学(IHC)标志物。然而,它的特异性不高,对三阴性乳腺癌(TNBC)的敏感性很低。SOX-10 和 trichorhinophalangeal 综合征 1 型(TRPS-1)已被建议纳入 TNBC 的诊断。TRPS-1 尚未在细胞学标本中确立为转移性乳腺癌(MBC)的诊断 IHC 标志物。因此,在本研究中,我们评估了 TRPS-1 在诊断细胞学标本中的 MBC 的应用价值。
纳入 2020 年 1 月至 10 月间细胞学标本诊断为 MBC 的病例。仅纳入有激素状态且细胞块上有≥20 个肿瘤细胞的病例。评估细胞块的 TRPS-1、GATA-3 和 SOX-10 IHC 标志物阳性(强度和肿瘤细胞百分比)。结果与标本类型(细针抽吸[FNA]与体液)和各种 BC 预后亚组相关联。
我们分析了 61 例病例,包括 33 例体液和 28 例 FNA(13 例淋巴结、10 例骨、2 例肝、2 例软组织和 1 例肺)标本。TRPS-1 在 ER/PR+(雌激素受体/孕激素受体阳性)MBC 中的阳性率为 97.2%,GATA-3 在同一组中的阳性率为 100%。TRPS-1 在 37 例中的 35 例(94.6%)中呈高度阳性,1 例(2.6%)呈中度阳性,1 例(2.7%)呈阴性/弱阳性。相比之下,GATA-3 在所有 37 例中均呈高度阳性。SOX-10 在 37 例中仅 1 例(2.7%)呈阳性,呈中度阳性。在 HER2+(人类表皮生长因子受体 2 阳性)组中,TRPS-1 在 7 例中的 5 例(71.4%)呈高度阳性,1 例(14.3%)呈中度阳性,1 例(14.3%)呈阴性/弱阳性。然而,GATA-3 在 7 例中的 6 例(85.7%)呈高度阳性,1 例(14.3%)呈阴性/弱阳性。SOX-10 在所有 7 例中均呈阴性。在 TNBC 中,TRPS-1 在 17 例中的 16 例(94%)呈高度阳性,1 例(5.9%)呈中度阳性,GATA-3 在 9 例(53%)中呈高度阳性,2 例(11.8%)呈中度阳性,6 例(35.3%)呈弱阳性/阴性。在阳性病例数量(P=0.07)、肿瘤细胞阳性百分比(P=0.005)和反应强度(P=0.005)方面,TRPS-1 的表达明显高于 GATA-3。SOX-10 在 17 例中仅 5 例(29%)表达,肿瘤细胞阳性百分比平均为 26.5%,反应强度为 0.8。在任何一组中,不同标本类型(FNA 与体液)之间的 IHC 结果均无差异。
TRPS-1 是一种高度敏感的新的乳腺癌诊断 IHC 标志物,在 ER/PR+和 HER2+BC 中的阳性率与 GATA-3 相似,在 TNBC 中的阳性率高于 GATA-3 和 SOX-10。特别是当细胞块上只有少数簇肿瘤细胞时,TRPS-1 非常有用,因为它的肿瘤细胞阳性百分比和强度均高于其他 IHC 标志物。